linezolid in the treatment of hemodialysis patients with catheter-related gram-positive bloodstream infections

Conditions: Bacteremia; Gram-Positive Bacterial Infections

Summary: this study will treat hemodialysis patients who have a central catheter that is thought to be infected with a specific bacteria (gram positive bacteria).

pfizer suspended enrollment on 21 august 2006 as a precautionary measure in light of the mortality imbalance seen in a similar study, and terminated the study on april 6, 2007 due to factors affecting the timeline to completion, such as slow enrollment and inclusion of sufficient evaluable subjects.

Eligibility criteria:
inclusion criteria: * to be eligible for this study, a patient must provide informed consent and must meet all of the following criteria. no study procedures, including any baseline tests, should be performed until the patient (or parent/legally acceptable representative, if appropriate) legally signs the informed consent form. * male or female, 18 years of age or older and \>= 40 kg body weight * end-stage renal disease patients on hemodialysis with: a) signs and symptoms of a localized catheter-related infection (eg tenderness and/or pain, erythema, swelling, purulent exudates within 2 cm of entry site); or b) a body temperature of \>= 38.0 c or \< 36.0 c (oral equivalent); or c) a gram-positive blood culture. if the gram-positive isolate is s. aureus, it must be cultured from at least 1 culture bottle from either the peripheral set or the catheter set of culture bottles. for all other gram-positive pathogens (eg, coagulase-negative staphylococci), isolates need to be cultured from at least 2 culture bottles of which one must be from the peripheral set. there must be no other obvious source of the bacteremia * presence of at least one of the following systemic signs of infection (may be obtained up to 24 hours prior to baseline): \*hypotension, defined as systolic blood pressure \ = 40 mmhg from the patient's baseline, in the absence of other causes for hypotension; \*tachycardia defined as a pulse rate \> 90 beats per minute; \*tachypnea defined as a respiratory rate \> 20 breaths per minute or paco2 \ 10,000 cells/mm3 or \ 10% band neutrophil forms. * patients on hemodialysis with tunneled or nontunneled catheters including antibiotic coated hemodialysis catheters. patients may have more than one concurrent catheter. * patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures exclusion criteria: * patients presenting with any of the following will not be included in this study: * catheter-related bloodstream infections caused by gram-negative bacteria, fungi, mixed cultures of gram negative bacteria and gram positive bacteria or mixed cultures of gram positive/negative bacteria and fungi * patients with evidence of other infections resulting in bacteremia, such as clinical or radiographic signs of osteomyelitis, endocarditis, skin/skin structure infection, pneumonia, urinary tract infection, joint infection, intraabdominal infection, septic thrombophlebitis or other infection * patients in whom the infected catheter cannot be removed * patients with permanent intravascular devices such as artificial vascular grafts, implantable pacemakers or defibrillators; intra-aortic balloon pumps, and left ventricular assist device; intravascular transplants such as prosthetic cardiac valves; or non-intravascular devices such as peritoneal dialysis catheters; or neurosurgical devices such as ventriculo-peritoneal shunts, intra-cranial pressure monitors, or epidural catheters, prosthetic cardiac valves, prosthetic vascular grafts, or other internal prosthesis * females of child-bearing potential who are unable or unwilling to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant * identification of a pathogen resistant to linezolid or vancomycin * patients who are unlikely to survive through the treatment period and evaluation * administration of a glycopeptide antibiotic within 5 days prior to enrollment. administration of other potentially effective systemic gram-positive antibiotics for more than 48 hours within 72 hours prior to enrollment unless the pathogen showed drug resistance * previous enrollment in this protocol * hypersensitivity to linezolid, vancomycin, gentamicin or one of their excipients (or aztreonam if non-bacteremic gram-negative coverage is required) * concurrent use of another investigational medication or use within 30 days of study entry * patients with pressor and fluid-resistant hemodynamic compromise or pulmonary embolism